L-citrulline, or simply citrulline, is an α-amino acid, with its name derived from citrullus, the Latin word for watermelon. Citrulline is a key intermediate in the urea cycle, the pathway by which mammals excrete ammonia by converting it into urea. Citrulline is also produced as a byproduct of the enzymatic production of nitric oxide from the amino acid arginine, catalyzed by nitric oxide synthase.
Citrulline boosts nitric oxide (NO) production in the body. Nitric oxide helps arteries relax and work better, which improves blood flow throughout the body. NO is an integral part of the inflammatory phase, functioning as a regulatory mechanism to mediate epithelialization, angiogenesis, and collagen deposition crucial to the proliferative phase. NO-induced vasodilatation acted as a host-protective agent by killing pathogens and by increasing blood flow to wounds. The supplement of citrulline is used to lower blood pressure in people with prehypertension. Citrulline supplements may also ease symptoms of mild-to-moderate erectile dysfunction (ED) and help to address blood vessel problems such as slow wound healing due to diabetes.
Bodybuilders use citrulline malate, a formulation of L-citrulline with malic acid added, as a supplement. It is hypothesized that citrulline malate can increase NO and growth hormone synthesis, and can therefore promote improvements in athletic performance and physical energy levels. Such performance enhancement effects of citrulline, however, lack clinical validation.